In former smokers, "suppressing" chemopreventive agents, i.e. agents which have chemopreventive activity when given after the carcinogen, would appear to most useful. We have established that strain A mice exposed for five months to tobacco smoke and then kept for another four months in air develop significantly more lung tumors than do animals kept in air. We further have shown that a diet containing a mixture of myoinositol (10 g/kg diet) and dexamethasone (0.5 mg/kg diet) successfully prevents lung tumor development in mice exposed to tobacco smoke. The chemopreventive regimen is even effective when the animals are fed the myoinositol-dexamethasone diet once they have been removed from the smoke atmosphere. Thus we have an animal model that mimics "former smokers" and where other suppressing chemopreventive agents or treatment modes may be evaluated. Since myoinositol is a food constituent with no known toxicity, it will be explored whether myoinositol alone, fed in the diet, will give chemoprevention to mice that have "quit" smoking. In a second series of experiments we will examine whether the topical administration to the tissues of the respiratory tract of other suppressing agents (budesonide- epigallocatechin gallate (EGCG), isotretinoin, or lovastatin) may increase their efficacy while at the same time reducing their potential systemic toxicity in mice previously exposed to tobacco smoke. Eventually, these preclinical studies in an animal model of "former smokers" will help to evaluate the potential usefulness and also possible dosage regimens of chemopreventive agents characterized by their suppressing action.